CAR T-cell therapy makes ageing guts heal themselves
Immune cells are most commonly engineered to kill cancers, but now, scientists have shown the technique makes the gut lining of older mice resemble that of younger mice, raising hopes that the same approach could work in people
A robust gut lining is important for our overall health
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As we age, the cells that line our intestine gradually lose their ability to renew themselves, which is important for maintaining good immune health. But now, scientists have reversed this process in older mice using genetically engineered immune cells.
Known as CAR T-cell therapy, this is most commonly used to treat some kinds of blood cancer. This involves collecting a sample of someone’s immune cells, called T-cells, reprogramming them in the laboratory to target and kill cancer cells, multiplying them, and then infusing them back into the bloodstream. Variations on the technique have also recently shown potential for treating solid tumours, as well as for preventing clogged arteries and treating the autoimmune condition lupus.
In this latest study, Semir Beyaz at Cold Spring Harbor Laboratory in New York state and his colleagues wondered about the therapy’s potential for restoring function in an ageing intestine. They wanted to target senescent cells. These cells, which accumulate with age, have lost their ability to divide but remain metabolically active, releasing chemicals that promote inflammation and accelerate further ageing. To get to them, the team targeted a protein called uPAR, which is enriched on the surface of senescent cells.
“The decline we see in the ageing gut is a deficit in the fitness of the stem cells that renew the inner lining of the gut every three to five days,” says Beyaz. “We hypothesised that removal of the ‘unfit’ senescent cells would boost the regenerative capacity and fitness of the stem cells in old mice.”
To test this idea, the researchers engineered CAR T-cells in older mice to recognise uPAR on senescent cells and remove them. After the engineered cells were infused back into the mice, they observed that this restored the activity and number of their stem cells that maintain tissue function to levels that resemble younger mice. It also improved markers of gut barrier integrity and inflammation in these older mice to a greater extent than in another group of older mice that received CAR T-cell therapy that didn’t specifically target uPAR.